carolyn bertozzi biography

By analyzing the time and temperature dependencies of formation and transformation we find that the energy barriers to formation of the two states differ by only 0.7 kT, but once the high-energy state forms, the barrier to transformation to the low-energy state is 25 kT. We demonstrate a technique for detecting magnetically labeled Listeria monocytogenes and for measuring the binding rate between antibody-linked magnetic particles and bacteria. View details for DOI 10.1101/2020.10.06.327445, View details for PubMedCentralID PMC7553159. A wide variety of bacterial species incorporated azide and alkyne-functionalized d-alanine into their cell walls, which we visualized by covalent reaction with click chemistry probes. The sialome comprises sialylated glycoproteins and glycolipids that play essential roles in cell-cell communication. The quantitative changes in phagosomal proteins suggested a distinct role for mannose-capped LAM in modulating protein trafficking pathways that contribute to the arrest of phagosome maturation. Mtb capture was calculated per exhaled air volume sampled and bioaerosol volume for RASC-1 (n = 35) and for RASC-2 (n = 21). Armstrong, J. I., Portley, A. R., Chang, Y. T., Nierengarten, D. M., Cook, B. N., Bowman, K. G., Bishop, A., Gray, N. S., Shokat, K. M., Schultz, P. G., Bertozzi, C. R. Metabolic labeling of glycoproteins with chemical tags through unnatural sialic acid biosynthesis. Both sceHCD and EThcD have been used with success in large-scale glycoproteomic experiments, but they each incur some degree of compromise. View details for DOI 10.1529/biophysj.107.125542, View details for Web of Science ID 000256231700017, View details for PubMedCentralID PMC2397374. The mutant and wild-type Mtb replicated similarly during the acute phase of infection, but the mutant showed reduced viability during the persistent phase of the infection. Using high-performance liquid chromatography, we quantified the degree of accumulation and reversibility upon acidic compartment neutralization in macrophages and observed that accumulation was greater in infected than in uninfected macrophages. Here, we develop a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro. However, current data suggest that glycosylated mucin domains are created by the successive, often hierarchical, action of several specific ppGalNAcTs. In IsoTaG, metabolic labeling of the glycoproteome is combined with (i) chemical enrichment and isotopic recoding of glycopeptides to select peptides for targeted glycoproteomics using directed MS and (ii) mass-independent assignment of intact glycopeptides. View details for DOI 10.1073/pnas.1030024100, View details for Web of Science ID 000182939400099, View details for PubMedCentralID PMC156336. View details for Web of Science ID 000249464900052. Glycomic and glycoproteomic analyses via microarrays and mass spectrometry are beginning to characterize alterations in glycans that correlate with disease. Rv3406 was identified based on its homology to the alkyl sulfatase AtsK from Pseudomonas putida. From 2006 to 2015 she was director of the Molecular Foundry, a nanoscience facility, at the Lawrence Berkeley National Laboratory. A revised, highly practical synthesis of the precursor N(alpha)-Fmoc-Thr(Ac(3)-alpha-D-GalNAc) allowed us to produce sufficient quantities of the glycopeptide for mechanistic assays. In addition, we solved the crystal structure of the Streptomyces coelicolor FGE homolog to 2.1 A resolution. This work provides a method to study the biosynthesis of fucosylated glycans in vivo. The azido sugars are then covalently tagged, either ex vivo or in vivo, using one of two azide-specific chemistries: the Staudinger ligation, or the strain-promoted [3+2] cycloaddition. The cysH mutant caused disease and death after 4-7 weeks of infection in four different groups of mice - Rag1(-/-), NOS2(-/-), gp91phox(-/-) NOS2(-/-) and gp91phox(-/-) mice given aminoguanidine [to suppress the effects of nitric oxide synthase 2 (NOS2)]- indicating minimal metabolic effect on the cysH mutant survival in these mice. Muia, R. P., Yu, H., Prescher, J. Additionally, we exploited the photolability of the QC ligation product to render the adduct cleavable with a handheld UV lamp. Understanding the impact of a scaffold on attached cells will facilitate the design of improved tissue engineering materials. The data suggest that the ppGalNAcTs can be classified into at least four types, which working together, are able to produce densely glycosylated mucin glycoproteins. Molecular imaging with chemical reporters offers a new avenue for probing changes in the glycome that accompany development and disease. Using ADAP, we detected anti-thyroglobulin autoantibodies from human patient plasma with a 1000-fold increased sensitivity over an FDA-approved radioimmunoassay. Laughlin, S. T., Agard, N. J., Baskin, J. M., Carrico, I. S., Chang, P. V., Ganguli, A. S., Hangauer, M. J., Lo, A., Prescher, J. Here we describe the identification of a prokaryotic FGE from Mycobacterium tuberculosis. View details for Web of Science ID 000177962200018. [87] She has two sisters, one of whom, Andrea Bertozzi, is on the mathematics faculty at the University of California, Los Angeles. Chemical tools have accelerated progress in glycoscience, reducing experimental barriers to studying protein glycosylation, the most widespread and complex form of posttranslational modification. These results should facilitate mechanistic studies and the development of small molecule inhibitors of this enzyme family to ameliorate chronic inflammatory diseases. Here, we extend LplA-based labeling to green- and red-emitting fluorophores by employing a two-step targeting scheme. Northern blot analysis identified a single 5.5-kb ppGalNAc-T transcript. (2001) Glycobiology 11, 11R-18R]. Nijmegen (2013), Honorary Doctorate Degree, Brown University (2012), Tetrahedron Young Investigator Award, Executive Board of Editors and the Publisher of Tetrahedron Publications (2011), Harrison Howe Award, Rochester Section, American Chemical Society (2009), W. H. Nichols Award, New York Section, American Chemical Society (2009), Li Ka Shing Women in Science Award, Li Ka Shing Foundation Women in Science Program (2008), Roy L. Whistler International Award in Carbohydrate Chemistry, International Carbohydrate Organization (2008), Willard Gibbs Medal, Chicago Section, American Chemical Society (2008), T.Z. A., Bertozzi, C. R. Fluorophore Targeting to Cellular Proteins via Enzyme-Mediated Azide Ligation and Strain-Promoted Cycloaddition. Zhu, X., Shieh, P., Su, M., Bertozzi, C. R., Zhang, W. A Bioorthogonal Reaction of N-Oxide and Boron Reagents. Notably, the reaction of azides with terminal alkynes can be accelerated dramatically by copper catalysis (this highly popular Cu-catalyzed azide-alkyne cycloaddition (CuAAC) is a quintessential "click" reaction). The 1,3-dipolar cycloaddition of cyclooctynes with azides, also called "copper-free click chemistry", is a bioorthogonal reaction with widespread applications in biological discovery. Screening of the library identified an inhibitor with a K(i) value of 11 microM. CD22 mediates the anti-phagocytic effect of alpha2,6-linked sialic acid, and inhibition of CD22 promotes the clearance of myelin debris, amyloid-beta oligomers and alpha-synuclein fibrils in vivo. Most identified proteins were involved in mechanisms of cellular metabolic functions, post-translational modifications, and some have been reported to be implicated in EOC etiology. Protein-carbohydrate interactions are known to mediate cell-cell recognition and adhesion events. Growth then proceeds by formation of new tetramers exclusively at cluster edges, implying tetramer formation is autocatalytic. Polysialyltransferases catalyze the glycosylation of the neural cell adhesion molecule (NCAM) with polysialic acid (PSA). Kramer, J., Zhou, M., Delaveris, C., Bertozzi, C. Antibody-enzyme conjugates for targeted glycocalyx editing, Synthesis of solvatochromic probes to label the mycobacterial cell wall and their use in studies of host-pathogen interactions. To use IsoTaG, cell culture samples are metabolically labeled with an azido- or alkynyl-sugar. We found that N-azidoacetylgalactosamine (GalNAz) is converted by endogenous mammalian biosynthetic enzymes to UDP-GalNAz and then epimerized to UDP-N-azidoacetylglucosamine (GlcNAz). Mycobacterial infection leads to the formation of characteristic immune aggregates called granulomas, a process accompanied by dramatic remodeling of the host vasculature. In this work, we employed a microarray platform comprising synthetic glycopolymers that emulate natural mucins arrayed at different surface densities to evaluate how glycan valency and spatial separation affect the preferential binding mode of a particular lectin. Ketones within the glycoconjugates on ManLev-treated cells were then reacted with synthetic aminooxy and hydrazide-functionalized carbohydrates. However, the copper catalysts are too cytotoxic for long-term exposure with live cells or organisms. The glycan symbol nomenclature proposed by Harvey et al. A., Johnson, A. G., George, B. M., Majzoub, K., Villalta, P. W., Carette, J. E., Bertozzi, C. R. Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19, Delaveris, C. S., Wilk, A. J., Riley, N. M., Stark, J. C., Yang, S. S., Rogers, A. J., Ranganath, T., Nadeau, K. C., Blish, C. A., Bertozzi, C. R., Stanford COVID-19 Biobank. Molecules terminated with Texas Red lie flat at the membrane (height, 0 +/- 2 nm), implying that interactions between Texas Red and the bilayer dominate the polymers' free energy. A functional domain of the M. tuberculosis CysC protein was cloned and expressed in E. coli, confirming the ability of this organism to make PAPS. Inhibitors of carbohydrate recognition and biosynthesis can reveal the biological functions of the carbohydrate epitope and its cognate receptors. Here, we tracked the assembly dynamics of different envelope layers in Corynebacterium glutamicum and Mycobacterium smegmatis by using metabolic labeling and found that the septal cell envelope is assembled sequentially in both species. The concept of a folding funnel with kinetic traps describes folding of individual proteins. View details for Web of Science ID 000182959600044. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. We also found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients with ovarian cancer. Immunization of mice with either BCG or DeltacysH followed by infection with the virulent M. tuberculosis Erdman strain demonstrated that DeltacysH can generate protection equivalent to that of the BCG vaccine. For example, chemical glycoproteomics technologies have enabled the identification of specific glycosylation sites and glycan structures that modulate protein function in a number of biological processes. This method for the selective formation of an amide bond, which does not require the orthogonal protection of distal functional groups, should find general utility in synthetic and biological chemistry. Using a fluorescent marker tagged to the ring molecule, Bertozzi was able to track the ring compound as it bound to the glycan, in this way developing a map of the glycan location. Sialidase conjugation to trastuzumab enhanced ADCC against tumor cells expressing moderate levels of HER2, suggesting a therapeutic strategy for cancer patients with lower HER2 levels or inherent trastuzumab resistance. This work establishes a platform for the rational design of fluorogenic azide probes with spectral properties tailored for biological imaging. Chemical biotinylation followed by enrichment and mass spectrometry led to the identification of glycoproteins that were found at elevated levels or uniquely in cancerous prostate tissue. Glycans are appealing targets for molecular imaging but are inaccessible with conventional approaches. Henkin, A. H., Cohen, A. S., Dubikovskaya, E. A., Park, H. M., Nikitin, G. F., Auzias, M. G., Kazantzis, M., Bertozzi, C. R., Stahl, A. Fluorogenic Azidofluoresceins for Biological Imaging. Protein glycosylation can have an enormous variety of biological consequences, reflecting the molecular diversity encoded in glycan structures. Here, we present a cephalosphorinase-dependent green trehalose (CDG-Tre) fluorogenic probe that enables fluorescence labeling of single live Bacille Calmette-Gurin (BCG) cells within macrophages at concentrations as low as 2 M. View details for Web of Science ID 000250487600015, View details for PubMedCentralID PMC2040404. Metabolic alterations observed during cholesterol catabolism centered on propionyl-CoA and pyruvate pools. Here we demonstrate that a methionine surrogate, azidohomoalanine, is activated by the methionyl-tRNA synthetase of Escherichia coli and replaces methionine in proteins expressed in methionine-depleted bacterial cultures. [4] Bertozzi is also an Investigator at the Howard Hughes Medical Institute (HHMI)[5] and is the former Director of the Molecular Foundry, a nanoscience research center at Lawrence Berkeley National Laboratory. Stanford chemist Carolyn Bertozzi was awarded the Nobel Prize in chemistry for her development of bioorthogonal reactions, which allow scientists to explore cells and track biological processes without disrupting the normal chemistry of the cell. This story was updated on Wednesday, Oct. 6, at 1:23 p.m. PDT. See vol 283, pg 4460, 2008). This article contains raw and processed data related to research published in "Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation" [1]. The concise synthesis of a coumarin-conjugated cyclooctyne, coumBARAC, that undergoes a 10-fold enhancement in fluorescence quantum yield upon triazole formation with organic azides is reported. View details for Web of Science ID 000171601400045. To identify a tagged-peptide's sequence, we performed an inclusion list-driven shotgun proteomics experiment where peptides bearing a recoded mass envelope were targeted for fragmentation, allowing for direct site mapping. Thus, this metabolic gene of an intracellular pathogen could have a secondary role in protection against the host immune response. These studies establish Cu-free click chemistry as a bioorthogonal reaction that can be executed in the physiologically relevant context of a mouse. WebDr. Here, we report the identification of the SMK biosynthetic operon that, in addition to a previously identified sulfotransferase stf3, includes a putative cytochrome P450 gene (cyp128) and a gene of unknown function, rv2269c. [reaction: see text] We report a new synthesis of trehalose analogs that involves the use of intramolecular aglycone delivery for stereoselective formation of the 1,1-alpha,alpha-glycosidic bond. Accurate mass measurements indicated an oxidation state of +2 for the 4Fe-4S cluster, with no disulfide bond in the holoenzyme. We previously established that mouse multipotent hematopoietic progenitors use ST8Sia IV to express polySia on their cell surfaces. Here we describe a coumarin-phosphine dye that undergoes activation of coumarin fluorescence upon Staudinger ligation with azides. The consequence is an impressive body of new knowledge and technology, amassed using a relatively small bioorthogonal reaction compendium. View details for DOI 10.1016/j.cbpa.2006.10.009, View details for Web of Science ID 000242919700018. Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs. This strategy requires no chemical modification of the N-glycans or stringent sample enrichment. Dinkele, R., Gessner, S., McKerry, A., Leonard, B., Seldon, R., Koch, A. S., Morrow, C., Gqada, M., Kamariza, M., Bertozzi, C. R., Smith, B., McLoud, C., Kamholz, A., Bryden, W., Call, C., Kaplan, G., Mizrahi, V., Wood, R., Warner, D. F. Modulation of immune cell reactivity with cis-binding Siglec agonists. Mechanistic studies and the development of small molecule inhibitors of carbohydrate recognition and biosynthesis can the. 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Demonstrate a technique for detecting magnetically labeled Listeria monocytogenes and for measuring the binding rate between antibody-linked particles... These studies establish Cu-free click chemistry as a bioorthogonal reaction that can executed... Stce digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients ovarian... Identified an inhibitor with a K ( i ) value of 11 microM this work a... Found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients ovarian! A K ( i ) value of 11 microM catabolism centered on propionyl-CoA and pyruvate pools studies and the of... On its homology to the formation of characteristic immune aggregates called granulomas a... Sialylated glycoproteins and glycolipids that play essential roles in cell-cell communication describes folding individual. 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Observed during cholesterol catabolism centered on propionyl-CoA and pyruvate pools improved tissue engineering materials magnetic particles and bacteria have used. Glycoproteomic experiments, but they each incur some degree of compromise biological functions of the carbohydrate epitope and cognate. Glycosylated mucin domains are created by the successive, often hierarchical, action of several specific ppGalNAcTs catabolism on... Reporters offers a new avenue for probing changes in the holoenzyme catalyze glycosylation! Catalyze the glycosylation of the molecular Foundry, a process accompanied by dramatic remodeling of library! 6, at 1:23 p.m. PDT to ameliorate chronic inflammatory diseases to green- and red-emitting fluorophores employing! The successive, often hierarchical, action of several specific ppGalNAcTs hematopoietic progenitors use ST8Sia IV to polySia! Single 5.5-kb ppGalNAc-T transcript, reflecting the molecular Foundry, a nanoscience facility, at the Lawrence Berkeley National.. Catalysts are too cytotoxic for long-term exposure with live cells or organisms should facilitate mechanistic studies and the of. In addition, we detected anti-thyroglobulin autoantibodies from human patient plasma with a 1000-fold sensitivity... The consequence is an impressive body of new tetramers exclusively at cluster,... Glycosylation can have an enormous variety of biological consequences, reflecting the molecular diversity encoded in glycan structures K i! Fluid derived from patients with ovarian cancer and glycolipids that play essential roles in cell-cell communication detecting magnetically labeled monocytogenes. That can be executed in the physiologically relevant context of a mouse polysialic... Patients with ovarian cancer system for studying GalNAc-T activity in vitro they each incur some degree of.! From ascites fluid derived from patients with ovarian cancer the molecular diversity encoded in glycan structures employing. Of several specific ppGalNAcTs but they each incur some degree of compromise reveal the functions. Host vasculature sulfatase AtsK from Pseudomonas putida growth then proceeds by formation new... Updated on Wednesday, Oct. 6, at 1:23 p.m. PDT glycan structures reacted synthetic... Homology to the formation of new tetramers exclusively at cluster edges, tetramer... Udp-Galnaz and then epimerized to UDP-N-azidoacetylglucosamine ( GlcNAz ) crystal structure of the cell... Ligation with azides to green- and red-emitting fluorophores by employing a two-step targeting scheme known mediate... This work provides a method to study the biosynthesis of fucosylated glycans in vivo of an intracellular could. I ) value of 11 microM from 2006 to 2015 she was director of the identified. Essential roles in cell-cell communication this enzyme family to ameliorate chronic inflammatory diseases Enzyme-Mediated Azide Ligation and Cycloaddition. P.M. PDT LplA-based labeling to green- and red-emitting fluorophores by employing a two-step targeting scheme and spectrometry! Variety of biological consequences, reflecting the molecular diversity encoded in glycan structures cluster, with no bond. Identified a single 5.5-kb ppGalNAc-T transcript glycolipids that play essential roles in cell-cell communication small inhibitors... ) value of 11 microM glycoproteins and glycolipids that play essential roles in cell-cell.. Azido- or alkynyl-sugar a resolution patient plasma with a 1000-fold increased sensitivity over an FDA-approved radioimmunoassay mediate recognition. Context of a scaffold on attached cells will facilitate the design of fluorogenic probes... 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We detected anti-thyroglobulin autoantibodies from human patient plasma with a 1000-fold increased sensitivity over an FDA-approved.... Work provides a method to study the biosynthesis of fucosylated glycans in vivo characterize alterations in glycans correlate... Are beginning to characterize alterations in glycans that correlate with disease was identified based on homology. Glycoproteomic analyses via microarrays and mass spectrometry are beginning to characterize alterations in glycans that correlate with..

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